Transgenic TIEG non-human animals

Abstract

Materials and methods related to a transgenic non-human animal (e.g., a transgenic non-human mammal) whose genome comprises a disrupted TIEG allele are provided. Methods for making such transgenic non-human animals, and using them to identify and characterize agents that affect conditions related to TIEG activity, such as cardiac hypertrophy and bone formation also are provided. In addition, materials and methods related to the treatment of hypertrophic cardiomyopathy are provided.

1. A transgenic mouse whose genome comprises a disruption of an endogenous transforming growth factor-β-inducible early gene (TIEG) nucleic acid, wherein:
 (a) said mouse is homozygous for said disruption, is a male mouse, and develops cardiac hypertrophy, 
 (b) said mouse is homozygous for said disruption and is a female mouse, wherein male progeny of said female mouse that are homozygous for said disruption develop cardiac hypertrophy, or 
 (c) said mouse is heterozygous for said disruption, and wherein male progeny of said mouse that are homozygous for said disruption develop cardiac hypertrophy. 
 
     
     
       2. The transgenic mouse of  claim 1 , wherein the genetic background of said mouse is selected from the group consisting of B6, 129Sv/J, and FVB. 
     
     
       3. The transgenic mouse of  claim 1 , wherein said mouse is a male mouse and is homozygous for said disruption. 
     
     
       4. The transgenic mouse of  claim 3 , wherein said mouse exhibits a symptom of human hypertrophic cardiomyopathy. 
     
     
       5. The transgenic mouse of  claim 1 , wherein said disruption results from deletion of a portion of the endogenous TIEG gene. 
     
     
       6. The transgenic mouse of  claim 5 , wherein exons 1 and 2 of said endogenous TIEG are deleted. 
     
     
       7. Progeny of the transgenic mouse of  claim 1 , wherein said progeny comprise a disruption of an endogenous TIEG gene. 
     
     
       8. Cells isolated from the transgenic mouse of  claim 1 . 
     
     
       9. The cells of  claim 8 , wherein said cells are cardiomyocytes, osteoblasts, or osteoclasts.